Studies designed to elucidate the functions of two types of adenylate cyclase of brain are in progress. One form is regulated by Ca2 ion and a specific calcium-binding regulatory protein (CDR); the second form is CA2 ion independent. The distribution of the two forms with respect to brain regions and among various cell types will be examined. Reconstitution of catecholamine receptors, CA2 ion, CDR and adenylate cyclase into a functionally coupled complex will be attempted. Possible alterations in chromatin structure and function associated with cyclic GMP-dependent phosphorylation of nuclear proteins will be studied in neurons, glia and glial tumor cell lines in culture. Immunohistochemical techniques for the localization of cyclic AMP and cyclic GMP will be utilized in certain of these studies.